Most drug abusers use alcohol in addition to their primary drug of abuse, yet little is known about the behavioral pharmacology of such combinations. The specific purpose of this project is to experimentally analyze in human volunteers the behavioral and physiological effects of prototypical stimulant drugs of abuse in combination with alcohol. The acute effects of varying doses of cocaine, damphetamine nicotine and caffeine will be examined in combination with alcohol under controlled laboratory conditions. The following routes of drug administration will be used: cocaine, intranasal and oral; d-amphetamine, oral; nicotine, oral; caffeine, oral; alcohol, oral. Two experiments using withinsubject repeated-measures designs are proposed for each of the stimulantalcohol combinations. First, the direct effects of each stimulant and alcohol will be determined alone and in combination on behavioral measures (repeated acquisition of behavioral chains, digit symbol substitution task, circular lights) selfreport (Addiction Research Center Inventory, visualanalogue scales) and physiological measures (pupil diameter, cardiovascular measures). Second, the effects of pretreatment with varying doses of the stimulant compounds on alcohol selfadministration will be examined. The studies proposed in this application will provide the first experimental investigations of stimulant-alcohol combinations in humans where (a) doses of both compounds are varied alone and in combination, (b) behavioral, selfreport, and physiological measures are obtained, and (c) effects on drug selfadministration are examined. Results from these studies will contribute to our basic understanding of the human behavioral pharmacology of acute stimulantalcohol interactions and provide important practical information concerning the behavioral and physiological toxicity of such combinations.